Protein structure dynamic nature

Frauenfelder H, Petsko GA, TSemoglou D (1979) Tfemperature-dependent X-ray diffraction as a probe of protein structural dynamics. Nature (Lond) 280 558-563... 

Frank, I. M. and Vavilov, S. I, 1931. Uber die WirkungssphSre der Ausldschungsvargange in den flureszierenden fliissigkeiten. Z. Phys. 69, 100 - 110. Franzen, L. E., Svensson, S. and Farm, O, 1980, Structural studies on the carbohydrate portion of human antithrombin III. Journal of Biological Chemistry. 255, 5090-5093. Frauenfelder, H., Petsko, C.A., and Tsernoglou, D, 1979, Temperature-dependent X-ray diffraction of a probe of protein structural dynamics. Nature 280, 558-563. 

Depending on external conditions (pH, temperature, composition of solution) and molecular structure (changes of protein structure upon natural or artificial mutations), equilibrium between different conformers can be dynamic. During enzymatic reaction the excited LO (LO ) is generated in the active site of each conformer. Initially there is a mixture of complexes ... 

The essential role of protein structure dynamics as a mechanistic consideration in proton transport has focused attention on amino acids such as proline (3, 9), which can confer localized flexibility within and between helical segments. Except for the unique case of bacteriorhodopsin, which is amenable to spectroscopic examination (10), little is known about the nature of molecular dynamics in transport enzymes. 

This text is similar to that of McCammon and Harvey (see below), but also provides a background for force field-based calculations and a more sophisticated discussion. Includes numerous examples of computing the structure, dynamics, and thermodynamics of proteins. The authors provide an interesting chapter on the complementary nature of molecular mechanics calculations and specific experimental techniques. 

In addition to the described above methods, there are computational QM-MM (quantum mechanics-classic mechanics) methods in progress of development. They allow prediction and understanding of solvatochromism and fluorescence characteristics of dyes that are situated in various molecular structures changing electrical properties on nanoscale. Their electronic transitions and according microscopic structures are calculated using QM coupled to the point charges with Coulombic potentials. It is very important that in typical QM-MM simulations, no dielectric constant is involved Orientational dielectric effects come naturally from reorientation and translation of the elements of the system on the pathway of attaining the equilibrium. Dynamics of such complex systems as proteins embedded in natural environment may be revealed with femtosecond time resolution. In more detail, this topic is analyzed in this volume [76]. 

Noncovalent interactions play a key role in biodisciplines. A celebrated example is the secondary structure of proteins. The 20 natural amino acids are each characterized by different structures with more or less acidic or basic, hydrophilic or hydrophobic functionalities and thus capable of different intermolecular interactions. Due to the formation of hydrogen bonds between nearby C=0 and N-H groups, protein polypeptide backbones can be twisted into a-helixes, even in the gas phase in the absence of any solvent." A protein function is determined more directly by its three-dimensional structure and dynamics than by its sequence of amino acids. Three-dimensional structures are strongly influenced by weak non-covalent interactions between side functionalities, but the central importance of these weak interactions is by no means limited to structural effects. Life relies on biological specificity, which arises from the fact that individual biomolecules communicate through non-covalent interactions." " Molecular and chiral recognition rely on... 

The newly evolving ideas of a protein differ from those that can be generated from the X-ray structure mainly because they are dynamic and not static in nature. Nuclear magnetic resonance spectroscopy (nmr) is the technique that is revealing the most detail about the dynamic aspects of protein structure, and much of this article is concerned with the results of nmr studies. It is unfortunately the case that dynamic models are much the more difficult to describe and to use in a precise way, but it is very important to realize that quite a new outlook on a protein has to be developed. The dynamics of a protein structure are now known to be specific to a given protein, and the response of the protein to external changes, either physical or chemical, is therefore specific also. 

Other spectroscopic methods cannot provide the same overall picture of protein structure or dynamics. However, they can give information about specific atoms or groups in the protein. In order to gain detailed information from these techniques, it is generally necessary to study metal atoms, which in some cases are a natural part of the protein and in other cases may be specifically introduced. Techniques such as UV, visible, Raman, and epr spectroscopies provide information about the metal atom and its environment, which is concerned both with structural features and with energetic features. 

Frye and Edidin provided a striking visual demonstration of the dynamic nature of membrane structure. They labeled proteins on the plasma membranes of two samples of cells with fluorescent dyes, human cells with a dye that emitted red light, and mouse cells with a dye that emitted green light (fig. 17.15). The two populations of cells then were mixed and treated with Sendai virus, which causes individual cells to fuse. Immediately after the fusion, red fluorescence from the human proteins could be seen on one half of the hybrid membrane, and green fluorescence from the mouse proteins on the other half. But within a few min, the two types of proteins were intermingled over the entire surface. 

The complex suite of membrane lipids would seem to create a potential for localized variation in lipid composition around specific membrane proteins. The roles played by such lipid domains are an area of active research (Williams, 1998). In view of the dynamic nature of membrane structure, however, it is extremely difficult experimentally to isolate and characterize small regions of the bilayer. Despite these difficulties, investigators of fine-scale membrane... 

Derivatives of compound (1) are of interest because they are aza analogues of indoles which are commonly found in natural alkaloids and synthetic pharmaceutical preparations <90MI 706-01). Compound (1) has been used as a chromophoric moiety in 7-azatryptophan, an optical probe useful in the study of protein structure and dynamics <92JA8343>. Benzo derivatives such as the partial structure (113) have been used as tryptophan mimics (B-89MI706-01). 

This Chapter will highlight some of the features relating to the structure and construction of supramolecular structures that are primarily protein based. Examples of supramolecular structures found outside cells (extracellular matrices) and within cells (cytoskeletal networks) will be given that emphasize the relationships between the structure and function of these networks, the role of their frequently dynamic nature, and the genetic and congenital errors that can lead to, or be associated with, disease. 

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